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Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice

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Abstract

Chemotherapy is an integral part of modern day treatment regimen but anticancer drugs fail to demarcate between cancerous and normal cells thereby causing severe form of systemic toxicity. Among which pulmonary toxicity is a dreadful complication developed in cancer patients upon cyclophosphamide (CP) therapy. Oxidative stress, fibrosis, and apoptosis are the major patho-mechanisms involved in CP-induced pulmonary toxicity. In the present study, we have synthesized Nano-Se, nanotechnology-based new form of elemental selenium which has significantly lower toxicity and acceptable bioavailability. In order to meet the need of effective drugs against CP-induced adverse effects, nano selenium (Nano-Se) was tested for its possible protective efficacy on CP-induced pulmonary toxicity and bone marrow toxicity. CP intoxication resulted in structural and functional lung impairment which was revealed by massive histopathological changes. Lung injury was associated with oxidative stress/lipid peroxidation as evident by increased in reactive oxygen species, nitric oxide level, and malondialdehyde (MDA) formation with decreased in level of antioxidants such as reduced glutathione, glutathione-S-transferase, glutathione peroxidase, superoxide dismutase, and catalase. Furthermore, CP at a dose of 25 mg/kg b.w. increased pulmonary DNA damage (‘comet tail’) and triggered DNA fragmentation and apoptosis in mouse bone marrow cells. On the other hand, Nano-Se at a dose of 2 mg Se/kg b.w., significantly inhibited CP-induced DNA damage in bronchoalveolar lavage cells, and decreased the apoptosis and percentage of DNA fragmentation in bone marrow cells and also antagonized the reduction of the activities of antioxidant enzymes and the increase level of MDA. Thus, our results suggest that Nano-Se in pre- and co-administration may serve as a promising preventive strategy against CP-induced pulmonary toxicity.

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Acknowledgements

This work was financially supported by Grant from Indian Council of Medical Research, New Delhi, India (no. 45/36/2008/PHA-BMS). Arin Bhattacharjee gratefully acknowledges ICMR for Senior Research Fellowship. Abhishek Basu also gratefully acknowledges ICMR for Senior Research Fellowship (no. 3/2/2/58/2011/NCD-III). The authors wish to thank the Director, CNCI, for supporting this study.

Compliance with Ethical Standards

The entire experiments were carried out strictly following compliance with the ethical standards and guidelines of Institutional Animal Ethics Committee [Committee for the Purpose of Control and Supervision of Experiment on Animals, India].

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Cancer Chemoprevention, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, West Bengal, India

    Arin Bhattacharjee, Abhishek Basu & Sudin Bhattacharya

  2. Department of Translational Research, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, West Bengal, India

    Jaydip Biswas

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  1. Arin Bhattacharjee
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  2. Abhishek Basu
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Correspondence to Sudin Bhattacharya.

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Bhattacharjee, A., Basu, A., Biswas, J. et al. Nano-Se attenuates cyclophosphamide-induced pulmonary injury through modulation of oxidative stress and DNA damage in Swiss albino mice. Mol Cell Biochem 405, 243–256 (2015). https://doi.org/10.1007/s11010-015-2415-1

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